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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 梁祥光 | zh_TW |
| dc.contributor.advisor | Hsiang-Kuang Liang | en |
| dc.contributor.author | 鞠佩恩 | zh_TW |
| dc.contributor.author | Pei-An Chu | en |
| dc.date.accessioned | 2024-07-30T16:16:22Z | - |
| dc.date.available | 2024-07-31 | - |
| dc.date.copyright | 2024-07-30 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-07-16 | - |
| dc.identifier.citation | 1. Perkins, A. and G. Liu, Primary brain tumors in adults: diagnosis and treatment. American family physician, 2016. 93(3): p. 211-217B.
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Rezaei-Tavirani, M., et al., TiO2 nanoparticle as a sensitizer drug in radiotherapy: in vitro study. International Journal of Cancer Management, 2013. 6(Supplement). 47. Maher, E.A., et al., Malignant glioma: genetics and biology of a grave matter. Genes & development, 2001. 15(11): p. 1311-1333. 48. Omuro, A. and L.M. DeAngelis, Glioblastoma and other malignant gliomas: a clinical review. Jama, 2013. 310(17): p. 1842-1850. 49. Niyazi, M., et al., Therapeutic options for recurrent malignant glioma. Radiotherapy and Oncology, 2011. 98(1): p. 1-14. 50. Zucker, R., et al., Detection of TiO2 nanoparticles in cells by flow cytometry. Cytometry Part A, 2010. 77(7): p. 677-685. 51. Moriyama, A., et al., Oxidative stress caused by TiO2 nanoparticles under UV irradiation is due to UV irradiation not through nanoparticles. Chem Biol Interact, 2018. 294: p. 144-150. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/93389 | - |
| dc.description.abstract | 惡性膠質瘤是一種高度侵襲性的腦癌，其死亡率相當高，而存活率相對較低。目前，治療惡性膠質瘤的標準方法包括手術、放射治療和抗癌藥物的結合，然而，這些治療方式仍存在挑戰。首先，血腦障壁使得靜脈注射之治療藥物難以有效地到達腦中腫瘤部位。其次，正常腦組織的耐受性限制了可給予的放射劑量。本研究中，我們希望探討將二氧化鈦奈米粒子與紫外光及放射治療結合使用，透過其效力和便利性，以促進對惡性膠質瘤的協同效應。二氧化鈦奈米粒子具有獨特的性質，使其在各種應用中具有優勢，但此材料也能與生物系統相互作用，透過光刺激誘導活性氧的生成。然而，二氧化鈦奈米粒子結合紫外光與放射治療照射惡性膠質瘤的抗癌效果尚未確定，本研究旨在利用上述治療模式，探討協同增強其抗癌的效果。在我們的研究中，使用ALTS1C1細胞和各類動物模型來驗證二氧化鈦奈米粒子結合紫外光與放射治療的抗癌效果。研究顯示，二氧化鈦奈米粒子對惡性膠質瘤細胞既具有光增敏劑又具有放射增敏劑的作用。它通過生成活性氧來誘導DNA鏈斷裂，最終導致細胞凋亡。透過小鼠腫瘤模型的體內實驗，我們證實了局部藥物傳輸搭載二氧化鈦奈米粒子的凝膠合併紫外光與放射治療，不僅能透過協同抗癌效果有效抑制腫瘤生長，還在活體中顯示高生物相容性。 | zh_TW |
| dc.description.abstract | Malignant gliomas are associated with a highly aggressive form of brain cancer. The death rate for malignant gliomas, is unfortunately quite high, and the survival rates are relatively low. At present, the standard approach to treatment of malignant gliomas involves the combination of surgery, radiotherapy (RT) and anticancer agents, yet there are challenges exist in this treatment modality. Firstly, the blood-brain barrier (BBB) acts as a hindrance, making it challenging to deliver therapeutic agents effectively to the tumor site. Secondly, the tolerance of normal brain tissue sets a constraint on the overall radiation dosage that can be administered. In this study, we would like to investigate the effectiveness and convenience of treatment, combing titanium dioxide (TiO2) nanoparticles with ultraviolet (UV) irradiation and RT to facilitate the synergistic effect for malignant gliomas. TiO2 nanoparticles have unique properties that make them useful in various applications, but they can also interact with biological systems, potentially leading to the generation of reaction oxygen species (ROS). However, the anticancer effect on malignant gliomas of TiO2 combined with UV irradiation and RT remained undetermined. This research aims to employ TiO2 to synergistically enhance the anticancer effects when combined with both radiation and UV irradiation. In our study, we utilized ALTS1C1 cells and animal tumor models to demonstrate the anticancer effect of combined treatment of TiO2 along with UV irradiation and RT. Our observations indicate that TiO2 serves as both photosensitizer and radiosensitizer for glioma cells. It inhibits tumor proliferation by inducing DNA strand break through the generation of ROS, ultimately resulting in apoptosis. Trough in vivo experiment by mouse tumor model, we proved that the combination treatment involving TiO2-loaded CMC gel, UV irradiation, and RT can not only effectively inhibits tumor growth by synergistic anticancer effects but also exhibits biocompatibility in living body. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-07-30T16:16:22Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-07-30T16:16:22Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員審定書 I
致謝 II 中文摘要 III Abstract IV Table of Contents VI LIST OF FIGURES XI List of Abbreviations 1 1.1 Epidemiology and pathology of malignant gliomas 1 1.2 Current treatment 2 1.3 Synergistic effect of drug combined with UV irradiation and RT 3 3.2 In vitro 24 3.2.1 Microscope images analysis TiO2 nanoparticles were uptake by ALTS1C1 cells 24 3.2.2 Flow cytometry analysis TiO2 nanoparticles were uptake by ALTS1C1 cells 25 3.2.3 TiO2 inhibited the proliferation of ALTS1C1 cells 25 3.2.4 TiO2 shows synergistic effect in ALTS1C1 cells together with UV irradiation or RT 26 3.2.5 TiO2 induced ALTS1C1 cells death 29 3.2.6 TiO2 increases intracellular ROS level 30 3.2.7 TiO2 induced DNA strand break of ALTS1C1 cells 32 3.2.8 TiO2 promotes apoptosis of ALTS1C1 cells 34 1.4 Local drug delivery 4 1.5 TiO2 nanoparticles 5 1.6 Purpose of study 6 Chapter 2 Material and Methods 8 2.1 Biomaterial 8 2.1.1 Preparation of TiO2-loaded CMC gel 8 2.1.2 Biocompatibility of the TiO2-loaded CMC gel 8 2.1.3 Gel degradation and drug release profile of TiO2 8 2.2 In vitro 9 2.2.1 Cell culture 9 2.2.2 Cellular uptake (Micrograph) 9 2.2.3 Cellular uptake (Flow cytometry) 9 2.2.4 Cell viability assay 10 2.2.5 Colony formation assay 10 2.2.6 Live and dead assay 11 2.2.7 Oxidative stress assay 12 2.2.8 DNA strand break assay 12 2.2.9 Apoptosis assay 13 2.2.10 UV irradiation of cell 14 2.2.11 RT irradiation of cell 14 2.3 In vivo 15 2.3.1 In vivo investigation 15 2.3.2 Subcutaneous tumor implant mouse model 15 2.3.2.1 Intratumoral injection in subcutaneous tumor implant mouse model 15 2.3.2.2 UV irradiation of subcutaneous tumor implant mouse model 15 2.3.2.3 RT Irradiation of subcutaneous tumor implant mouse model 16 2.3.2.4 Tumor volume measurements of subcutaneous tumor implant mouse model 16 2.3.2.5 Body weight measurements of subcutaneous tumor implant mouse model 16 2.3.2.6 Evaluation of treatment effect by gross examination of tumors in subcutaneous tumor implant mouse model 16 2.3.3 Biocompatibility mouse model 17 2.3.3.1 Intratumoral injection in biocompatibility mouse model 17 2.3.3.2 UV irradiation of biocompatibility mouse model 17 2.3.3.3 RT Irradiation of biocompatibility mouse model 18 2.3.3.4 Body weight measurements of biocompatibility mouse model 18 2.3.3.5 Biocompatibility evaluation by blood analysis and brain, liver, kidney gross in biocompatibility mouse model 18 2.3.4 Intracranial tumor implant mouse model 19 2.3.4.1 Intratumoral injection in intracranial tumor mouse model 19 2.3.4.2 UV irradiation of intracranial tumor mouse model 19 2.3.4.3 RT Irradiation of intracranial tumor mouse model 20 2.3.4.4 Tumor growth measurements of intracranial tumor implant mouse model 20 2.3.4.5 Body weight measurements of intracranial tumor mouse model 20 2.3.4.6 Evaluation of treatment effect by gross examination of tumors in intracranial tumor mouse model 20 2.4 Statistical analysis 21 Chapter 3 Results 22 3.1 Biomaterial 22 3.1.1 Biocompatibility of the TiO2-loaded CMC gel 22 3.1.2 Degradation of CMC gel 22 3.1.3 Drug release profile of TiO2-loaded CMC gel 23 3.3 In vivo 35 3.3.1 Subcutaneous tumor implant mouse model 35 3.3.1.1 Effectiveness of TiO2-loaded CMC gel combined with UV irradiation and RT for tumor growth control of subcutaneous tumor implant mouse model 35 3.3.1.2 Safety of combination of TiO2-loaded CMC gel with UV irradiation and RT of subcutaneous tumor implant mouse model 36 3.3.1.3 Histological Analysis of tumors after treatment in subcutaneous tumor implant mouse model 37 3.3.2 Biocompatibility mouse model 38 3.3.2.1 Safety of combination of TiO2-loaded CMC gel with UV irradiation and RT in biocompatibility mouse model 38 3.3.2.2 Histological Analysis of brain after treatment in biocompatibility mouse model 38 3.3.2.3 Biocompatibility evaluation by blood analysis after treatment in biocompatibility mouse model 39 3.3.3 Intracranial tumor implant mouse model 39 3.3.3.1 Tumor growth evaluation by BLI of intracranial tumor implant mouse model 39 3.3.3.2 Safety of combination of TiO2-loaded CMC gel with UV irradiation and RT in intracranial tumor implant mouse model 41 3.3.3.3 Histological Analysis of brain tissue and tumors after treatment in intracranial tumor implant mouse model 41 Chapter 4 Discussion 43 Chapter 5 Conclusion And Future Prospect 47 Supplementary Data 48 1. TiO2 shows the biocompatibility of 3T3 cells 48 2. Survival rate of combination of TiO2-loaded CMC gel with UV irradiation and RT in biocompatibility mouse model 49 3. Histological Analysis of liver and kidney after treatment in biocompatibility mouse model 49 Reference 51 | - |
| dc.language.iso | en | - |
| dc.subject | 放射治療 | zh_TW |
| dc.subject | 紫外光 | zh_TW |
| dc.subject | 局部藥物傳輸 | zh_TW |
| dc.subject | 惡性膠質瘤 | zh_TW |
| dc.subject | 二氧化鈦奈米粒子 | zh_TW |
| dc.subject | 活性氧激活 | zh_TW |
| dc.subject | Malignant gliomas | en |
| dc.subject | Reaction oxygen species activation | en |
| dc.subject | Ultraviolet irradiation | en |
| dc.subject | Radiation therapy | en |
| dc.subject | TiO2 nanoparticle | en |
| dc.subject | Local delivery | en |
| dc.title | 局部藥物傳輸搭載二氧化鈦奈米粒子的凝膠合併紫外光與放射治療增強對惡性膠質瘤的協同抗癌作用 | zh_TW |
| dc.title | Combing local delivery of nano-TiO2-loaded gel with ultraviolet and X-ray irradiation to enhance anticancer effects for malignant gliomas | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 趙本秀;黃楓婷 | zh_TW |
| dc.contributor.oralexamcommittee | Pen-Hsiu Chao;Feng-Ting Huang | en |
| dc.subject.keyword | 惡性膠質瘤,二氧化鈦奈米粒子,紫外光,放射治療,活性氧激活,局部藥物傳輸, | zh_TW |
| dc.subject.keyword | Malignant gliomas,TiO2 nanoparticle,Radiation therapy,Ultraviolet irradiation,Reaction oxygen species activation,Local delivery, | en |
| dc.relation.page | 54 | - |
| dc.identifier.doi | 10.6342/NTU202401312 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2024-07-16 | - |
| dc.contributor.author-college | 工學院 | - |
| dc.contributor.author-dept | 醫學工程學系 | - |
| 顯示於系所單位： | 醫學工程學研究所 | |
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